The neurotoxins of proteolytic Clostridium botulinum cultures are dichains (mol wt 150,000) made of disulfide linked heavy (H chain; mol wt 100,000) and light (L chain; mol wt 50,000) subunits. Highly purified H chain of type A toxin has been recovered by the preferential precipitation of L chains by using NADH during reduction of disulfide bond of intact toxin. The complementary H and L chains of type B toxin can be separately purified. The work to be done will attempt the preparation of a neurotoxic hybrid molecule by combining the H chain of type A toxin with the L chain of type B toxin. When the L chain of type A toxin can be isolated, a similar attempt will be made to obtain a type-hybrid toxin made of L chain of A toxin and H chain of type B toxin. Studies will be done to identify the subunit of botulinum toxin that binds to nerve endings.